In many tumor types TAM infiltration level has been shown to be of significant prognostic value. TAMs have been linked to poor prognosis in breast cancer, ovarian cancer, types of glioma and lymphoma; better prognosis in colon and stomach cancers and both poor and better prognoses in lung and prostate cancers.

As one route to reducing TAMs CSF1R inhibitors have been developed as a possible cancer therapy and many are in early clinical trials. CSF1R inhibitors in clinical trials include : Pexidartinib, PLX7486, ARRY-382, JNJ-40346527, BLZ945, Emactuzumab, AMG820, IMC-CS4. (MCS110 is a CSF1 inhibitor)

Another CSF1R inhibitor that targets/depletes TAMs is Cabiralizumab (cabira; FPA-008) which is a monoclonal antibody and is in early clinical trials for metastatic pancreatic cancer.

Monocytosis is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states.

Examples of processes that can increase a monocyte count include:

- chronic inflammation

- stress response

- Cushing's syndrome (hyperadrenocorticism)

- immune-mediated disease

- granulomatous disease

- atherosclerosis

- necrosis

- red blood cell regeneration

- viral fever

- sarcoidosis

A high count of CD14+CD16++ monocytes is found in severe infection (sepsis)

In the field of atherosclerosis high numbers of the CD14++CD16+ intermediate monocytes were shown to be predictive of cardiovascular events in at risk populations.

Adipose tissue macrophages (abbr. ATMs) comprise tissue resident macrophages present in adipose tissue. Adipose tissue apart from adipocytes is composed of the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and variety of immune cells. The latter ones are composed of mast cells, eosinophils, B cells, T cells and macrophages. The number of macrophages within adipose tissue differs depending on the metabolic status. As discovered by Rudolph Leibel and Anthony Ferrante et al. in 2003 at Columbia University, the percentage of macrophages within adipose tissue ranges from 10% in lean mice and humans up to 50% in extremely obese, leptin deficient mice and almost 40% in obese humans. Increased number of adipose tissue macrophages correlates with increased adipose tissue production of proinflammatory molecules and might therefore contribute to the pathophysiological consequences of obesity (e.g. insulin resistance, type 2 diabetes).

Small image of an infected area of the body due to a reaction with an implant

A histiocyte is an animal cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyte is a tissue macrophage or a dendritic cell (histio, diminutive of histo, meaning "tissue", and cyte, meaning "cell").

Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self and foreign lipids and glycolipids. They constitute only approximately 0.1% of all blood T cells. Natural killer T cells should not be confused with natural killer cells.

Macrophages (pronunciation: /ˈmakrə(ʊ)feɪdʒ/ | , from Greek "μακρός" ("makrós") = large, "φαγείν" ("phageín") = to eat) are a type of white blood cell that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the types of proteins specific to healthy body cells on its surface in a process called phagocytosis. These large phagocytes are found in essentially all tissues, where they patrol for potential pathogens by amoeboid movement. They take various forms (with various names) throughout the body (e.g., histiocytes, Kupffer cells, alveolar macrophages, microglia, and others), but all are part of the mononuclear phagocyte system. Besides phagocytosis, they play a critical role in nonspecific defense (innate immunity) and also help initiate specific defense mechanisms (adaptive immunity) by recruiting other immune cells such as lymphocytes. For example, they are important as antigen presenters to T cells. In humans, dysfunctional macrophages cause severe diseases such as chronic granulomatous disease that result in frequent infections.

Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines. Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages. This difference is reflected in their metabolism; M1 macrophages have the unique ability to metabolize arginine to the "killer" molecule nitric oxide, whereas rodent M2 macrophages have the unique ability to metabolize arginine to the "repair" molecule ornithine. However, this dichotomy has been recently questioned as further complexity has been discovered.

Human macrophages are about in diameter and are produced by the differentiation of monocytes in tissues. They can be identified using flow cytometry or immunohistochemical staining by their specific expression of proteins such as CD14, CD40, CD11b, CD64, F4/80 (mice)/EMR1 (human), lysozyme M, MAC-1/MAC-3 and CD68.

Macrophages were first discovered by Élie Metchnikoff, a Russian zoologist, in 1884.

Foam cells are the fat-laden M2 macrophages that serve as the hallmark of early stage atherosclerotic lesion formation. They are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening.

Foam cell formation is triggered by a number of factors including the uncontrolled uptake of modified low density lipoproteins (LDL), the upregulation of cholesterol esterification and the impairment of mechanisms associated with cholesterol release. Foam cells are formed when circulating monocyte-derived cells are recruited to the atherosclerotic lesion site or fat deposits in the blood vessel walls. Recruitment is facilitated by the molecules P-selectin and E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). Monocytes are then able to penetrate the arterial wall as a result of impaired endothelial integrity which increases permeability. Once in the sub endothelium space, inflammation processes induce the differentiation of monocytes into mature macrophages. Macrophages are then able to internalize modified lipoproteins like βVLDL (beta very low density lipoprotein), AcLDL (acetylated low density lipoprotein) and OxLDL (oxidized low density lipoprotein), which are rich in cholesterol esters, through their binding to scavenger receptors (SR), CD36 and SR-A located on the macrophage surface. Coated-pit endocytosis, phagocytosis and pinocytosis are all responsible for lipoprotein internalization. Lipoproteins are transported to endosomes or liposomes for degradation, whereby the cholesteryl esters (CE) are hydrolyzed to unesterified free cholesterol (FC) by lysosomal acid lipase (LPL). Free cholesterol is transported to the endoplasmic reticulum where it is re-esterified by ACAT1 (acyl-CoA: cholesterol acyltransferase 1) and subsequently stored as cytoplasmic liquid droplets. These droplets are responsible for the foamy appearance of the macrophage and thus the name of foam cells. At this point, foam cells can either be degraded though the de-esterification and secretion of cholesterol, or can further promote foam cell development and plaque formation – a process that is dependent on the balance of free cholesterol and esterified cholesterol.

Low-density lipoprotein (LDL) and modified LDL cholesterol, also known as “bad” cholesterol, is contained by a foam cell - a marker of atherosclerosis. The uptake of LDL alone does not cause foam cell formation, however, the co-internalization of LDL with modified LDL in macrophages can result foam cell development. Modified LDL affects the intracellular trafficking and metabolism of native LDL, such that not all LDL need to be modified for foam cell formation when LDL levels are high.

Foam cell degradation or more specifically the breakdown of esterified cholesterols, is facilitated by a number of efflux receptors and pathways. Esterified cholesterol from cytoplasmic liquid droplets are once again hydrolyzed to free cholesterol by acid cholesterol esterase. Free cholesterol can then be secreted from the macrophage by the efflux to ApoA1 and ApoE discs via the ABCA1 receptor. This pathway is usually used by modified or pathological lipoproteins like AcLDL, OxLDL and βVLDL. FC can also be transported to a recycling compartment through the efflux to ApoA1 containing HDLs (high density lipoproteins) via aqueous diffusion or transport through the SR-B1 or ABCG1 receptors. While this pathway can also be used by modified lipoproteins, LDL derived cholesterol can only use this pathway to excrete FC. The differences in excretory pathways between types of lipoproteins is mainly a result of the cholesterol being segregated into different areas.

The maintenance of foam cells and the subsequent progression of plaque build-up is caused by the secretion of chemokines and cytokines from macrophages and foam cells. Foam cells secrete pro-inflammatory cytokines such as interleukins: IL-1, IL-6; tumour necrosis factor (TNF); chemokines: chemokines ligand 2, CCL5, CXC-chemokine ligand 1 (CXCL1); as well as macrophage retention factors. Macrophages within the atherosclerotic legion area have a decreased ability to migrate, which further promotes plaque formation as they are able to secrete cytokines, chemokines, reactive oxygen species (ROS) and growth factors that stimulate modified lipoprotein uptake and vascular smooth muscle cell (VSMC) proliferation. VSMC can also accumulate cholesteryl esters.

To summarize, in chronic hyperlipidemia, lipoproteins aggregate within the intima of blood vessels and become oxidized by the action of oxygen free radicals generated either by macrophages or endothelial cells. The macrophages engulf oxidized low-density lipoproteins (LDLs) by endocytosis via scavenger receptors, which are distinct from LDL receptors. The oxidized LDL accumulates in the macrophages and other phagocytes, which are then known as foam cells. Foam cells form the fatty streaks of the plaques of atheroma in the tunica intima of arteries.

Foam cells are not dangerous as such, but can become a problem when they accumulate at particular foci thus creating a necrotic centre of atherosclerosis. If the fibrous cap that prevents the necrotic centre from spilling into the lumen of a vessel ruptures, a thrombus can form which can lead to emboli occluding smaller vessels. The occlusion of small vessels results in ischemia, and contributes to stroke and myocardial infarction, two of the leading causes of cardiovascular-related death.

Foam cells are very small in size and can only be truly detected by examining a fatty plaque under a microscope after it is removed from the body, or more specifically from the heart. Detection usually involves the staining of sections of aortic sinus or artery with Oil Red O (ORO) followed by computer imaging and analysis; or from Nile Red Staining. In addition, flouresecnet microscopy or flow cytometry can be used to detect OxLDL uptake when OxLDL has been labeled with 1,1′-dioctadecyl-3,3,3′3′-tetra-methylindocyanide percholorate (DiL-OxLDL).

Autoimmunity occurs when the body starts attacking itself. The link between atherosclerosis and autoimmunity is plasmacytoid dendritic cells (pDCs). PDCs contribute to the early stages of the formation of atherosclerotic lesions in the blood vessels by releasing large quantities of type 1 interferons (INF). Stimulation of pDCs leads to an increase of macrophages present in plaques. However, during later stages of lesion progression, pDCs have been shown to have a protective effect by activating T cells and Treg function; leading to disease supression.

Foam cells may form around leaked silicone from breast implants, inhaled organic antigens and some drugs.

In medicine, desmoplasia is the growth of fibrous or connective tissue. It is also called desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.

Desmoplasia is usually only associated with malignant neoplasms, which can evoke a fibrosis response by invading healthy tissue. Invasive ductal carcinomas of the breast often have a scirrhous, stellate appearance caused by desmoplastic formations.

Monocytopenia is a form of leukopenia associated with a deficiency of monocytes.

A very low count of these cells is found after therapy with immuno-suppressive glucocorticoids.

Also, non-classical slan+ monocytes are strongly reduced in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), a neurologic disease associated

with mutations in the macrophage colony-stimulating factor receptor gene.

Lymphocyte-variant hypereosinophilia usually takes a benign and indolent course. Long term treatment with corticosteroids lowers blood eosinophil levels as well as suppresses and prevents complications of the disease in >80% of cases. However, signs and symptoms of the disease recur in virtually all cases if corticosteroid dosages are tapered in order to reduce the many adverse side effects of corticosteroids. Alternate treatments used to treat corticosteroid resistant disease or for use as corticosteroid-sparing substitutes include interferon-α or its analog, Peginterferon alfa-2a, Mepolizumab (an antibody directed against IL-5), Ciclosporin (an Immunosuppressive drug), imatinib (an inhibitor of tyrosine kinases; numerous tyrosine kinase cell signaling proteins are responsible for the growth and proliferation of eosinophils {see clonal eosinophilia}), methotrexate and Hydroxycarbamide (both are chemotherapy and immunosuppressant drugs), and Alemtuzumab (a antibody that binds to the CD52 antigen on mature lymphocytes thereby marking them for destruction by the body). The few patients who have been treated with these alternate drugs have exhibited good responses in the majority of instances. Reslizumab, a newly developed antibody directed against interleukin 5 that has been successfully used to treat 4 patients with the hypereosinophilic syndrome, may also be of use for lymphocyte-variant eosinophilia. Patients suffering minimal or no disease complications have gone untreated.

In 10% to 25% of patients, mostly 3 to 10 years after initical diagnosis, the indolent course of lymphocyte-variant hypereosinophilia changes. Patients exhibit rapid increases in lymphadenopathy, spleen size, and blood cell numbers, some cells of which take on the appearance of immature and/or malignant cells. Their disease soon thereafter escalates to an angioimmunoblastic T-cell lymphoma, peripheral T cell lymphoma, Anaplastic large-cell lymphoma (which unlike most lymphomas of this type is Anaplastic lymphoma kinase-negative), or Cutaneous T cell lymphoma. The malignantly transformed disease is aggressive and has a poor prognosis. Recommended treatment includes chemotherapy with Fludarabine, Cladribine, or the CHOP combination of drugs followed by bone marrow transplantation.

Lymphocyte-variant hypereosinophila, also termed lymphocyte variant eosinophilia, is a rare disorder in which eosinophilia or hypereosinophilia (i.e. a large or extremely large increase in the number of eosinophils in the blood circulation) is caused by aberrant population of lymphocytes. These aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of bone marrow eosinophil-precursor cells termed colony forming unit-Eosinophils or CFU-Eos.

The overly stimulated CFU-Eos cells mature to apparently normal eosinophils, enter the circulation, and may accumulate in, and severely damage, various tissues. The disorder is usually indolent or slowly progressive but may proceed to a leukemic phase and at this phases is sometimes classified as acute eosinophilic leukemia. Hence, lymphocyte-variant hypereosinophilia can be regarded as a precancerous disease.

The order merits therapeutic intervention to avoid or reduce eosinophil-induced tissue injury and to treat its leukemic phase. The latter phase of the disease is aggressive and typically responds relatively poorly to anti-leukemia chemotherapeutic drug regimens.

Research into AM functionality has been on the rise since AMs are one of the first lines of a defense against invasive pathogens. One of the most prominent fields is investigating liposomes as deliverers of antibiotics for treatment of respiratory intracellular infections. Intracellular parasites, such as M. tuberculosis, C. pneumoniae, L. monocytogenes, L. pneumophila, and F. tularensis, (to name a few) are taken up by AMs via phagocytosis, but are resistant to the biocidal mechanisms of AMs and can survive intracellularly, thus inducing severe respiratory infections. Pulmonary tuberculosis is caused by M. tuberculosis, and is now a major infectious disease worldwide and its incidence is increasing, especially in association with the AIDS pandemic. For sterilization of intracellular parasites in AMs, antibiotics are normally given orally or intravenously, but much of the antibiotics disperse to many different tissues, diminishing its effectiveness. Pulmonary administration of mannosylated liposomes is a much more direct, efficient route in targeting AMs; it enhances antimicrobial effect, reduces the dosage needed, and avoids unnecessary distribution to the blood. Since mannose receptors are exclusively expressed on the surface of AM, mannosylation of liposomes is an appealing approach to cell-selective targeting to AM. The efficacy of pulmonary administration of ciprofloxacin (CPFX) incorporated into mannosylated liposomes (mannosylated CPFX-lipososomes) was examined in rats, and determined to be an efficient means to target AMs.

Lymphoid hyperplasia is the rapid growth proliferation of normal cells that resemble lymph tissue.

Infection of macrophages in joints is associated with local inflammation during and after the acute phase of "Chikungunya" (caused by CHIKV or Chikungunya virus).

A foreign-body giant cell is a collection of fused macrophages (giant cell) which are generated in response to the presence of a large foreign body. This is particularly evident with implants that cause the body chronic inflammation and foreign body response.

This reaction to the implant causes damages to the infected area, leaving the exterior surface with scars.

The nuclei are arranged in a disorganized manner. The nuclei in this cell are centrally placed and overlap each other. This is in contrast to a Langhans giant cell, where the nuclei are arranged on the border.

Foreign body cells can detect and eliminate

bacteria caught within the body, by sensing the unique sugar coating that are

on the invading prokaryotes. These macrophage cells are one of a few

phagocytic cells, but not the first to come to an injury site, and tend to

linger from anytime between days to weeks. There has been some research done on other variations of

giant calls with different functions.

The Xanthogranulomatous Process (XP), also known as Xanthogranulomatous Inflammation is a form of acute and chronic inflammation characterized by an exuberant clustering of foamy macrophages among other inflammatory cells. Localization in the kidney and renal pelvis has been the most frequent and better known occurrence followed by that in the gallbladder but many others have been subsequently recorded. The pathological findings of the process and etiopathogenetic and clinical observations have been reviewed by Cozzutto and Carbone.

The term "NK T cells" was first used in mice to define a subset of T cells that expressed the natural killer (NK) cell-associated marker NK1.1 (CD161). It is now generally accepted that the term "NKT cells" refers to CD1d-restricted T cells, present in mice and humans, some of which coexpress a heavily biased, semi-invariant T-cell receptor and NK cell markers.

Macrophages within tumor stroma, so called tumor-associated macrophages (TAMs) promote tumor growth and metastasis. Tumor-associated macrophage infiltration correlates with poor prognosis in patients with breast, cervix, bladder and brain cancers. Pathophysiological interaction between tumor-associated macrophages and surrounding cells, such as endothelial cells promote tumor progression. In 1971, Judah Folkman proposed that angiogenesis plays essential role in tumor growth. Macrophages secrete many pro-angiogenic factors including vascular endothelial growth factor (VEGF), TNF-α, granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-1 and IL-6. Additionally it has been shown that adipose tissue surrounding certain tumors or metastases to the lymph nodes, which are embedded in adipose tissue, fuels tumor growth by serving as a depot for adipose tissue macrophages that stumulate angiogenesis and resemble TAMs.

It is one common source of appendicitis, as it may cause an obstruction of the appendiceal lumen, resulting in the subsequent filling of the appendix with mucus, causing it to distend and internal pressure to increase.

Xanthogranulomatous osteomyelitis (XO) is a peculiar aspect of osteomyelitis characterized by prevalent histiocytic infiltrate and foamy macrophage clustering.

Agranulocytes, also known as mononuclear leukocytes, are white blood cells with a one-lobed nucleus. They are characterized by the absence of granules in their cytoplasm, which distinguishes them from granulocytes. Normal hematologic blood values of MLs are about 35% of all white blood cells. The 2 types of agranulocytes in the blood circulation are lymphocytes and monocytes. A third type of agranulocyte, the macrophage, is formed in the tissue when monocytes leave the circulation and differentiate into macrophages.

Lymphocytes are much more common in the lymphatic system, and include natural killer T-cells. The blood has three types of lymphocytes: B cells, T cells and natural killer cells (NK cells). B cells make antibodies that bind to pathogens to enable their destruction. CD4+ (helper) T cells co-ordinate the immune response (they are what becomes defective in an HIV infection). CD8+ (cytotoxic) T cells and natural killer cells are able to kill cells of the body that are infected by a virus. T cells are crucial to the immune response because they possess a unique 'memory' system which allows them to remember past invaders and prevent disease when a similar invader is encountered again.

Monocytes share the "vacuum cleaner" (phagocytosis) function of neutrophils, but are much longer lived as they have an additional role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so that an antibody response may be mounted. Monocytes are also known as macrophages after they migrate from the bloodstream and enter tissue.

Other white blood cells which are not agranulocytes are mainly the granulocytes: neutrophils, eosinophils and basophils.

Histiocytes are derived from the bone marrow by multiplication from a stem cell. The derived cells migrate from the bone marrow to the blood as monocytes. They circulate through the body and enter various organs, where they undergo differentiation into histiocytes, which are part of the mononuclear phagocytic system (MPS).

However, the term "histiocyte" has been used for multiple purposes in the past, and some cells called "histocytes" do not appear to derive from monocytic-macrophage lines. (The term Histiocyte can also simply refer to a cell from monocyte origin outside the blood system, such as in a tissue (as in rheumatoid arthritis as palisading histiocytes surrounding fibrinoid necrosis of rheumatoid nodules).

Some sources consider Langerhans cell derivatives to be histiocytes. The Langerhans cell histiocytosis embeds this interpretation into its name.